Stanley J. Robboy

Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types.

One thousand consecutive cases of surgically proven endometriosis were reviewed to evaluate the frequency and types of pelvic cancers that were associated with ovarian and extraovarian endometriosis. The frequency and types of histologic abnormalities present in the eutopic endometrium when cancers were noted in endometriosis were also evaluated. In the large subset of cases for which the authors were the primary pathologists and all foci of endometriosis were recorded, the frequency of malignancy was 10.8%. In contrast, the frequency was only 3.2% in cases diagnosed by others previously in our institution. Cancers were more commonly found in ovaries when endometriosis was present in that ovary (5%) compared to when endometriosis was present at other sites (1%). Clear cell and endometrioid carcinomas were the malignancies most commonly seen in ovaries containing endometriosis, while clear cell adenocarcinoma and adenosarcoma were most commonly seen in conjunction with extraovarian endometriosis. The association of endometriosis with endometrioid and clear cell carcinoma was much stronger than that of serous and mucinous tumors (p < .01). Concurrent endometrial pathology was commonly seen in cases of malignant transformation of endometriosis (32% of cases).

Disseminated intravascular coagulation (DIC): An approach

Abstract The etiology of disseminated intravascular coagulation (DIC) can be classified into three processes: (1) endothelial cell injury which activates Hageman factor and the intrinsic clotting system, (2) tissue injury which activates the extrinsic clotting system, or (3) red cell or platelet injury with the release of coagulant phospholipids. These initiating mechanisms result in a final common product, thrombin, which cleaves fibrinogen, activates factor XIII, aggregates platelets, releases platelet constituents and triggers secondary fibrinolysis. Plasmin produces fibrinogen degradation products which participate in the hemorrhagic diathesis. Detection of these fragments provides a sensitive method of diagnosing DIC. DIC usually presents with bleeding at multiple sites, and occasionally with thrombotic episodes or acrocyanosis. The diagnostic manifestations of DIC include a hemorrhagic-thrombotic diathesis, a specific coagulation test profile, the presence of fibrin thrombi and the response to heparin therapy. Analysis of our large series of patients finds the presence of three abnormal screening tests to be diagnostic (prothrombin time, fibrinogen and platelets). If only two of the three are abnormal, a test for fibrinolysis (thrombin time, euglobulin clot lysis time or fibrinogen degradation products) should be abnormal in order to establish the diagnosis. Treatment with heparin usually results in decreased bleeding. The prothrombin time, fibrinogen level and euglobulin lysis become normal within one to three days in those who stop bleeding. The titer of fibrinogen degradation products may respond rapidly but if greatly elevated remains abnormal for more than a week. Platelet levels do not respond uniformly to heparin therapy; when they do respond, it frequently requires several weeks. Even severe fibrinolysis responds to heparin therapy and is probably always secondary to DIC. Epsilon aminocaproic acid (EACA) therapy alone aggravates DIC and often results in thrombosis.

Prenatal exposure to stilbestrol. A prospective comparison of exposed female offspring with unexposed controls.

Abstract The effects of prenatal exposure to diethylstilbestrol were studied by a prospective cohort investigation of 110 exposed and 82 unexposed females. The general health characteristics of mothers and daughters in both groups were similar. Among the exposed, there were striking benign alterations of the genital tract, which included transverse ridges (22 per cent), abnormal vaginal mucosa (56 per cent), and biopsy-proved adenosis (35 per cent). Among the unexposed there were no ridges and one case of vaginal mucosal abnormality including adenosis (p < 0.0001). Abnormal cervical epithelium occurred in almost all exposed subjects but in only half the unexposed (p < 0.0001). The incidence of vaginal adenosis was highest when diethylstilbestrol was begun in early pregnancy. It was not detected when treatment was initiated in the 18th week or later. Oral contraceptive use and prior pregnancy were associated with less adenosis and erosion, respectively (p <0.05). No cases of cancer were observed. (N Engl J...

Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol

BACKGROUND Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. METHODS We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. RESULTS Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. CONCLUSIONS In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix.

This study was based on cases accessioned in the Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females to ascertain the incidence of diethylstilbestrol (DES)-related cancers by age and year of birth. For accuracy in estimating the size of the reference population for the incidence rates, calculations were restricted to 127 white residents of the United States who were exposed prenatally to DES or other nonsteroidal synthetic estrogens. The disease is exceedingly rare prior to age 14 when the incidence rate begins to rise rapidly. The incidence peaks at age 19 (median 19.2 years) and then drops precipitately. Thus, DES-related clear cell adenocarcinoma is unusual in that nearly all cancers have been diagnosed in a narrow age range of 10 years (14 to 23 years). Women born in 1951 to 1953 have higher incidence rates than those born in the previous or subsequent three-year period. This suggests that the prevalence of pregnancy-related use of DES was at a peak in the early 1950s. The cumulative risk of this type of genital cancer, through age 24, for DES-exposed female subjects is estimated to be in the range of 0.14 to 1.4 per thousand. The wide limits are due to the fact that the number of young women exposed is not known precisly. The low risk of disease and the narrow age range of the cases, relative to the long latency period, suggest that DES is an incomplete carcinogen. Other factors, possibly related to puberty, may be involved in the causation of this disease.

Ovarian teratoma with glial implants on the peritoneum: An Analysis of 12 Cases

Abstract Twelve cases of ovarian teratoma with peritoneal implants composed exclusively or predominantly of mature glia were analyzed from a clinicopathologic viewpoint. The survival of all 12 patients, regardless of whether the treatment was simple removal of the primary tumor or a more extensive operation with additional radiation or chemotherapy, suggests that a conservative surgical approach without therapy directed at the implants is adequate to effect a cure.

Clear-cell adenocarcinoma of the vagina and cervix in girls: Analysis of 170 Registry cases ☆

Abstract One hundred cases of vaginal and 70 cervical adenocarcinomas from the Registry of Clear-Cell Adenocarcinoma of the Genital Tract in Young Females have been analyzed. The age range of the patients was 7 to 29 years, and the frequent association with prenatal exposure to diethylstilbestrol and similar nonsteroidal estrogens was confirmed. The hormone administration began prior to the eighteenth week of pregnancy and was continued for periods ranging from 1 week to almost the entire length of the pregnancy. The total dosages ranged from 300 to 18,200 mg. Although most patients had vaginal bleeding or discharge, 16 per cent were asymptomatic. Abnormal cytology was the first clue to the diagnosis of cancer in 11 patients, but 21 per cent of the smears were negative. The larger and more deeply invasive tumors were often complicated by lymph node metastases, but these were also encountered in 1 case in which the tumor had an area of only 3 sq. cm. and with another tumor that invaded less than 3 mm. These findings suggest that local treatment of the primary tumor alone may be inadequate in some cases. Recurrences developed in 37 of the patients and 24 of them died, although the follow-up in one third of the cases has been less than 2 years. The recurrences frequently involved the lungs and supraclavicular lymph nodes as well as the pelvis. The very common association of vaginal adenosis and the occasional coexistence of transverse vaginal or cervical ridges provide morphologic evidence of a stilbestrol-related disturbance in the development of the lower Mullerian tract. The results of intravenous pyelography suggest that the development of the urinary tract is not affected. The fact that all the asymptomatic patients with carcinoma have been successfully treated thus far underscores the importance of screening exposed asymptomatic patients in search of early cases. The rarity (9 per cent) of these cancers prior to the age of 12 years suggests that the inclusion of a large population of girls in this age group in a screening program would uncover very few cases. However, such individuals should certainly be examined at any time abnormal vaginal bleeding or discharge develops.

Autopsy Findings with Permanent Pervenous Pacemakers

Of 130 patients who received permanent pervenous pacemakers in the last 2 years at the Massachusetts General Hospital, 21 have died; complete postmortem data are available on seven who died 5 days to 18 months after insertion of the pacemaker. No deaths were related to pacemaker malfunction. No patient received routine anticoagulant therapy. The intracardiac portions of all pacemaker electrodes were 30 to 80% endothelialized. In three cases tiny, organized mural thrombi formed on these sheaths, but none appeared to give rise to pulmonary emboli. All pacemaker electrode tips were wedged firmly beneath the trabecular system of the right ventricular apex and elicited varying degrees of local fibrous tissue reaction. Further focal fibrotic attachments occurred in the right atrium and superior vena cava. Although in four cases the electrodes adhered to the chordae tendineae, the long-term presence of an electrode did not appear to compromise tricuspid valve function. Late removal of an electrode may be hazardous because of its firm attachments to the endocardium and tricuspid valve.

Insular carcinoid primary in the ovary A clinicopathologic analysis of 48 cases

Forty‐eight cases of primary insular carcinoid of the ovary were analyzed from a clinicopathologic viewpoint. Sixteen (33%) were associated with preoperative clinical evidence of the carcinoid syndrome. At operation only one ovary was usually enlarged, but in 16% the contralateral ovary was also enlarged by either a dermoid cyst or a mucinous cystadenoma or cystadenocarcinoma. The volume of the carcinoid was the most important determinant of whether the carcinoid syndrome was present. No patient had the syndrome whose carcinoid formed only a small portion of a teratoma. Pure tumors or components of teratomas between 4 and 7 cm in diameter were associated with the syndrome in one‐half, and larger carcinoids in two‐third of the cases. Prominent acinar differentiation also correlated with the presence of the syndrome. Although the prognosis was nearly always favorable after the removal of the tumor, tricuspid valve damage continued to progress and led to cardiac decompensation in one patient; fatal recurrences developed in two others. The primary insular carcinoid should be distinguished from carcinoid metastatic to the ovary, which is nearly always bilateral, is usually associated with the presence of peritoneal metastases, and has a poor prognosis.

Hepatoid yolk sac tumor of the ovary (Endodermal sinus tumor with hepatoid differentiation) : A light microscopic, ultrastructural and immunohistochemical study of seven cases

Seven cases of ovarian yolk sac tumor (endodermal sinus tumor) with patterns resembling those of hepatocellular carcinoma were encountered in patients 7–43 years of age. Two of the patients had gonadal dysgenesis with a 46XY karyotype. At operation three tumors were confined to the ovary and four were associated with intra‐abdominal metastases. Two of the Stage I tumors recurred within one year. The hepatoid pattern was a prominent feature of all the tumors and was exclusive in four of them. In one specimen it merged almost imperceptibly with a polyvesicular vitelline pattern. The hepatoid component of the tumors was characterized by discrete masses, nests and/or broad bands of large polyhedral cells with central nuclei and prominent nucleoli; gland‐like spaces, some of which contained mucin, were occasionally evident. Each tumor contained numerous PAS‐positive, diastase‐resistant intracytoplasmic and extracytoplasmic hyaline bodies. Alpha‐fetoprotein and alpha‐1‐antitrypsin were identified by immunoperoxidase and immunofluorescence techniques in four tumors and albumin in two. Immunoperoxidase stains for chorionic gonadotropin were negative in four cases. Ultrastructural analysis of two specimens disclosed features similar to those of hepatocellular carcinoma.